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| Fig. 1: Radiation therapist preps patient for radiation therapy. (Source: Wikimedia Commons) |
According to the St. Baldrick's Foundation, 300,000 children around the world receive cancer diagnoses each year. [1] Protocols have been established to treat different types of cancer, many of which involve a combination of surgical resection, chemotherapy agents, and radiation treatment (see Fig. 1). Ionizing radio-therapy can shrink tumors and treat the primary cancer, but can also induce mutations that result in cancers elsewhere in the body. Exposure to radiation has been identified as a cause of many types of cancer, so the ability of radiation treatment to cause secondary cancer comes as no surprise. [2] In survivors of childhood cancer, the 20- year cumulative incidence of a second malignancy is 3-4%; radiation-associated tumors comprise the most significant portion of these secondary cancers. [2] Beyond 20 years, these patients' risk of developing secondary malignancies continues to increase. The mortality and morbidity resulting from these secondary tumors causes suffering for patients and their families.
The decision whether to use radiation to treat childhood cancer can be difficult for physicians and families. Evidence indicates that pediatric cancer survivors can develop cancer later on due to these treatments, but often intensive radiation therapy is required to treat the cancer. [2] Researchers have explored the factors that mediate the risk of developing cancer following radiation therapy, identifying level of development of particular organs and body tissues, hormonal factors, and differences in disease manifestation between children and adults as relevant factors. [3] One review study examining a cohort of 14,358 childhood cancer survivors found a 30-year cumulative incidence of secondary malignancies of 9.3%. [3] In particular, female patients with a primary cancer of sarcoma or Hodgkin's lymphoma who received radiation treatment showed the highest risk of developing secondary cancer. [3] Furthermore, analysis revealed the incidence of certain secondary neoplasms to demonstrate dose-responsiveness according to dose of radiotherapy received.
Recent research has looked to identify what specific mutations tend to arise in secondary radiation therapy-induced tumors. These investigations have come after physicians have noted many long-term survivors of cancer in childhood developing a type of brain tumor called meningioma. To explore the differences between spontaneously-arising meningiomas and radiation-induced meningiomas, a group of researchers compared their genetic basis. [4] The group found a specific rearrangement of DNA in the radiation-induced tumors that differed from the mutations in the DNA causing spontaneous meningioma. As Dr. Ken Aldape explains, this finding is significant because it can inform treatment of children receiving brain and spinal cord radiation and potentially prevent them from developing these meningiomas in the first place.
Since its advent as a treatment for cancer, radiation therapy has been an essential weapon in the oncologist's arsenal. Its powerful tumor-killing effects make it a vital tool to shrink tumors, kill cancer cells, and cure patients. Its ability to alter biology at the cell level, however, gives radiation therapy the potential to damage DNA and create new mutations that result in uncontrolled cell growth. Radiation therapy is too powerful a treatment to give up; its use can be the difference between life and death for children with cancer. Therefore, research that reveals the specific mutations in radiation-induced tumors will be valuable going forward to inform screening and monitoring in pediatric cancer survivors and design therapies that could prevent secondary cancers from forming.
© Caroline Soane. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
[1] D. L. Stallings, "Shaved Heads Means More Dollars Donated for Children's Cancer Research," Ruidoso News, 8 Feb 18.
[2] A. K. Ng et al., "Secondary Malignancies Across the Age Spectrum," Semin. Radiat. Oncol. 20, 67 (2010).
[3] A. T. Meadows et al., "Second Neoplasms in Survivors of Childhood Cancer: Findings from the Childhood Cancer Survivor Study Cohort, "J. Clin. Oncol. 27, 2356 (2009).
[4] S. Agnihotri et al., "Therapeutic Radiation for Childhood Cancer Drives Structural Aberrations of NF2 in Meningiomas," Nat. Commun. 8, 186 (2017).
